Fig. 1.

A–D; Photomicrographs demonstrating the accumulation of cholesterol in the hippocampus (A, B) and cerebellum (C, D) of the 10-week-old Npc1^−/− (B, D) but not in control (Npc1^+/+; A, C) mice. E–L; Photomicrographs showing filipin labeling in astrocytes (red) in the hippocampus (E, F, I, J) and microglia (green) in the cerebellum (G, H, K, L) of 10-week-old control (Npc1^+/+; E, I, G, K) and Npc1^−/− (F, J, H, L) mice. Note that almost all microglia exhibit filipin labeling (arrows), whereas only few astrocytes displayed filipin staining. M–P; Photomicrographs depicting degenerating neurons in the cerebellum (O, P) but not in the hippocampus (M, N) of Npc1^−/− mice as revealed by Fluoro-Jade C staining. Q–T; Double immunofluorescence photomicrographs showing neurotrace (NT)/calbindin (CB) labeled neurons (red) and MAG-labeled myelinated fibers (green) in the hippocampus (Q, R) and cerebellum (S, T) of 10-week-old control (Npc1^+/+; Q, S) and Npc1^−/− (R, T) mouse brains. U–X; Immunoblots and respective histograms showing the altered levels of synaptophysin (SYN) and PSD-95 in the hippocampus (U, V) and cerebellum (W, X) of 4-, 7- and 10-week (wk) old Npc1^−/− mouse brains compared to age-matched controls (Npc1^+/+). Histograms represent quantification of data from three separate experiments, each of which was replicated 2–3 times. Py, pyramidal cell layer; Ml, molecular layer; Gcl, granular cell layer; Pcl, Purkinje cells. Scale bar = 50 µM. *p<0.05, **p<0.01.